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Review
. 2021 Oct 27;10(11):2914.
doi: 10.3390/cells10112914.

Two-Pore-Domain Potassium (K2P-) Channels: Cardiac Expression Patterns and Disease-Specific Remodelling Processes

Felix Wiedmann  1   2   3 , Norbert Frey  1   2   3 , Constanze Schmidt  1   2   3
Affiliations
Review

Two-Pore-Domain Potassium (K2P-) Channels: Cardiac Expression Patterns and Disease-Specific Remodelling Processes

Felix Wiedmann et al. Cells. .

Abstract

Two-pore-domain potassium (K2P-) channels conduct outward K+ currents that maintain the resting membrane potential and modulate action potential repolarization. Members of the K2P channel family are widely expressed among different human cell types and organs where they were shown to regulate important physiological processes. Their functional activity is controlled by a broad variety of different stimuli, like pH level, temperature, and mechanical stress but also by the presence of lipids or pharmacological agents. In patients suffering from cardiovascular diseases, alterations in K2P-channel expression and function have been observed, suggesting functional significance and a potential therapeutic role of these ion channels. For example, upregulation of atrial specific K2P3.1 (TASK-1) currents in atrial fibrillation (AF) patients was shown to contribute to atrial action potential duration shortening, a key feature of AF-associated atrial electrical remodelling. Therefore, targeting K2P3.1 (TASK-1) channels might constitute an intriguing strategy for AF treatment. Further, mechanoactive K2P2.1 (TREK-1) currents have been implicated in the development of cardiac hypertrophy, cardiac fibrosis and heart failure. Cardiovascular expression of other K2P channels has been described, functional evidence in cardiac tissue however remains sparse. In the present review, expression, function, and regulation of cardiovascular K2P channels are summarized and compared among different species. Remodelling patterns, observed in disease models are discussed and compared to findings from clinical patients to assess the therapeutic potential of K2P channels.

Keywords: K2P-channel; TASK-1; TREK-1; two-pore-domain potassium channel.

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Conflict of interest statement

F.W. and C.S. have filed patent applications for pharmacological and genetic targeting of cardiac TASK-1 channels for therapy of atrial arrhythmias.

Figures

Figure 1
Figure 1
Membrane topology and structure of K2P channels. K2P channel monomers (left), consisting of 4 transmembrane domains (M1–4) and 2 pore forming loops (P1–2) assemble as homo- or heterodimers. (right).
Figure 2
Figure 2
Cardiac mRNA levels of K2P channels in the human heart (whole tissue). Expression of two-pore-domain potassium (K2P-) channel mRNA level in human right atrial (n = 10) and left ventricular (n = 5) tissue samples. Data are given as mean ± SEM relative to the housekeeping gene importin 8 (IPO8). * indicate p < 0.05 from Student’s t-tests. Data from Schmidt et al. 2015, Circulation [8].
Figure 3
Figure 3
Potential translational implications of cardiac K2P channel expression.AF, atrial fibrillation; OSAS, obstructive sleep apnea; PAH pulmonary arterial hypertension; RVOT, right ventricular outflow tract; VF, ventricular fibrillation.
See this image and copyright information in PMC

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